Bupropion hydrochloride (Wellbutrin.RTM.) is a marketed antidepressant. It is chemically known as (.+-.)-2-(tert-butylamino)-3'-chloropropiophenone hydrochloride. (See U.S. Pat. Nos. 3,819,706 and 3,885,046 and the Merck Index, Eleventh Edition, entry No. 1488).
In usage, bupropion hydrochloride is sold in the form of an instant release tablet wherein greater than 75% of bupropion hydrochloride is released from the tablet into dissolution media in 45 minutes (See 1993 Physicians Desk Reference (PDR), pages 842 to 844). The PDR indicates bupropion hydrochloride as presently sold in an instant release tablet as being associated with seizures in approximately 0.4% (4/1000) patients treated at doses of up to 450 mg per day. In studies to date, the risk of seizures seem to be strongly associated, in part, with use of instant release tablets.
In order to reduce the seizure rate, it has been determined after experimentation that a controlled sustained release of bupropion hydrochloride should be employed.
Prior art with respect to this invention is to be found in U.S. Pat. No. 4,687,660 which discloses controlled sustained release tablets containing bupropion hydrochloride.
The present invention provides an improved product as well as ease of manufacture over that disclosed in U.S. Pat. No. 4,687,660.
After almost three years of work and testing, the present invention is now able to provide a controlled sustained release, sometimes also referred to as a sustained release (SR) tablet with improved properties and which has a shelf life over one year (i.e., there is less than 10% loss, most preferably less than about 5% loss (breakdown), of bupropion hydrochloride in one year) of storage at room temperature (59.degree. to 77.degree. C.) and 35 to 60% relative humidity. For example, with a tablet containing 100 mg of bupropion hydrochloride (label strength) the tablet will preferably contain no less than about 95 mg of bupropion hydrochloride after one year in storage (shelf life). As used herein, the term "tablet" includes the term "caplet", which is the word used to describe a tablet termed substantially in the shape of a capsule.
The oral administration of the controlled release tablets of this invention to treat depression in humans will be under the jurisdiction of the physician; however, tablets for a 150 pound human will ordinarily be given one to three times per day to provide a total daily dosage of 100 to 450 mg per day for a time period that the human patient requires same as determined by a physician. The tablets are swallowed by the human in the normal manner with the aid of water or other liquid. The tablets herein preferably have a round biconvex shape (which is preferred); however, this may be varied depending on the creativity of the tablet designer. With the tablets of this invention it is now possible to dose one or two times per day rather than the three times a day as presently done with the currently marketed product.